急性期ゲノムプロジェクト

集中治療室では、あらゆる原因によって生命の危機に瀕している重症患者の治療を行っています。そのような重症病態では、免疫が過剰に反応することから全身性炎症反応症候群を発症します。近年、遺伝子（DNA、RNA）や遺伝子産生物（たんぱく質、代謝産物）を網羅的に評価することが可能となってきました。本研究の目的は、網羅的分子情報に基づいて全身性炎症反応症候群の新規分子病態を解明することです。これから、将来的に個々の重症患者に最適な個別化医療の実現を目指します。

急性期ゲノムプロジェクトの業績一覧

1.Ito H, Ebihara T, Matsumoto H, Oda J. Relationship between growth differentiation factor 15 and functional prognosis and severity in traumatic brain injury. (Sci Rep. 2025; 15:2470). doi: https://doi.org/10.1038/s41598-025-87062-z

2.Sakakibara S, Liu YC, Ishikawa M, Edahiro R, Shirai Y, Haruna S, El Hussien MA, Xu Z, Li S, Yamaguchi Y, Murakami T, Morita T, Kato Y, Hirata H, Takeda Y, Sugihara F, Naito Y, Motooka D, Tsai CY, Ono C, Matsuura Y, Wing JB, Matsumoto H, Ogura H, Okada M, Kumanogoh A, Okada Y, Standley DM, Kikutani H, Okuzaki D. Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients. Life Sci Alliance. 2024 Sep 17;7(12):e202402774. doi: 10.26508/lsa.202402774. PMID: 39288992; PMCID: PMC11408605.

3.Okita T, Kita S, Fukuda S, Kondo Y, Sakaue TA, Iioka M, Fukuoka K, Kawada K, Nagao H, Obata Y, Fujishima Y, Ebihara T, Matsumoto H, Nakagawa S, Kimura T, Nishizawa H, Shimomura I. Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling. Biochem Biophys Res Commun. 2024 Nov 5;732:150403. doi: 10.1016/j.bbrc.2024.150403. Epub 2024 Jul 14. PMID: 39047402.

4.Muratsu A, Oda S, Onishi S, Yoshimura J, Matsumoto H, Togami Y, Mitsuyama Y, Ito H, Okuzaki D, Ogura H, Oda J. Bacterial sepsis causes more dramatic pathogenetic changes in the Th1 pathway than does viral (COVID-19) sepsis: a prospective observational study of whole blood transcriptomes. Virol J. 2024 Aug 19;21(1):190. doi: 10.1186/s12985-024-02451-6. PMID: 39160575; PMCID: PMC11334310.

5.Priest DG, Ebihara T, Tulyeu J, Søndergaard JN, Sakakibara S, Sugihara F, Nakao S, Togami Y, Yoshimura J, Ito H, Onishi S, Muratsu A, Mitsuyama Y, Ogura H, Oda J, Okusaki D, Matsumoto H, Wing JB. Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19. Nat Commun. 2024 Aug 9;15(1):6811. doi: 10.1038/s41467-024-50997-4. PMID: 39122676; PMCID: PMC11315995.

6.Metwally H, Elbrashy MM, Ozawa T, Okuyama K, White JT, Tulyeu J, Søndergaard N, Wing JB, Muratsu A, Matsumoto H, Ikawa M, Kishi H, Taniuchi I, Kishimoto T. Threonine phosphorylation of STAT1 restricts interferon signaling and promotes innate inflammatory responses. Proc Natl Acad Sci U S A. 2024 Apr23;121(17):e2402226121. doi: 10.1073/pnas.2402226121. Epub 2024 Apr 15. PMID: 38621137; PMCID: PMC11046697

7.Tachino J, Togami Y, Matsumoto H, Matsubara T, Seno S, Ogura H, Oda J. Plasma Proteomics Profile-Based Comparison of Torso Versus Brain Injury: A Prospective Cohort Study. J Trauma Acute Care Surg. 2024 Apr 10. doi:10.1097/TA.0000000000004356. Epub ahead of print. PMID: 38595266.

8.Mitsuyama Y, Matsumoto H, Togami Y, Oda S, Onishi S, Yoshimura J, Murtatsu A, Ito H, Ogura H, Okuzaki D, Oda J. T cell dysfunction in elderly ARDS patients based on miRNA and mRNA integration analysis. Front Immunol. 2024 Mar 20;15:1368446. doi: 10.3389/fimmu.2024.1368446. PMID: 38571958; PMCID: PMC10987699.

9.Tachino J, Seno S, Matsumoto H, Kitamura T, Hirayama A, Nakao S, Katayama Y, Ogura H, Oda J. Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan. Crit Care. 2024 Mar 19;28(1):89. doi: 10.1186/s13054-024-04871-w. PMID: 38504320; PMCID: PMC10953216.

10.Yoshimura J, Togami Y, Ebihara T, Matsumoto H, Mitsuyama Y, Sugihara F, Hirata H, Okuzaki D, Ogura H. Classification of patients with COVID-19 by blood RNA endotype: a prospective cohort study. Microbiol Spectr. 2023 Dec12;11(6):e0264523. doi: 10.1128/spectrum.02645-23. Epub 2023 Nov 15. PMID:37966347; PMCID: PMC10715063.

11.Kawakami E, Saiki N, Yoneyama Y, Moriya C, Maezawa M, Kawamura S, Kinebuchi A, Kono T, Funata M, Sakoda A, Kondo S, Ebihara T, Matsumoto H, Togami Y, Ogura H, Sugihara F, Okuzaki D, Kojima T, Deguchi S, Vallee S, McQuade S, Islam R,Natarajan M, Ishigaki H, Nakayama M, Nguyen CT, Kitagawa Y, Wu Y, Mori K, Hishiki T, Takasaki T, Itoh Y, Takayama K, Nio Y, Takebe T. Complement factor Dtargeting protects endotheliopathy in organoid and monkey models of COVID-19. Cell Stem Cell. 2023 Oct 5;30(10):1315-1330.e10. doi:10.1016/j.stem.2023.09.001. PMID: 37802037; PMCID: PMC10575686.

12.Kanki H, Matsumoto H, Togami Y, Okuzaki D, Ogura H, Sasaki T, Mochizuki H.Importance of microRNAs by mRNA-microRNA integration analysis in acute ischemic stroke patients. J Stroke Cerebrovasc Dis. 2023 Sep;32(9):107277. doi: 10.1016/j.jstrokecerebrovasdis.2023.107277. Epub 2023 Aug 8. PMID: 37562178.

13.Onishi S, Matsumoto H, Sugihara F, Ebihara T, Matsuura H, Osuka A, Okuzaki D,Ogura H, Oda J. Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome. iScience. 2023 Jul 3;26(8):107271. doi: 10.1016/j.isci.2023.107271. PMID: 37502255; PMCID: PMC10368932.

14.Inoue T, Shinnakasu R, Kawai C, Yamamoto H, Sakakibara S, Ono C, Itoh Y, Terooatea T, Yamashita K, Okamoto T, Hashii N, Ishii-Watabe A, Butler NS,
Matsuura Y, Matsumoto H, Otsuka S, Hiraoka K, Teshima T, Murakami M, Kurosaki T. Antibody feedback contributes to facilitating the development of Omicron- reactive memory B cells in SARS-CoV-2 mRNA vaccinees. J Exp Med. 2023 Feb 6;220(2):e20221786. doi: 10.1084/jem.20221786. Epub 2022 Dec 13. PMID: 36512034; PMCID: PMC9750191.

15.Ito H, Ishikawa M, Matsumoto H Sugihara F, Okuzaki D, Hirata H, Ogura H.Transcriptional differences between coronavirus disease 2019 and bacterial sepsis. Virol J. 2022 Nov 28;19(1):198. doi: 10.1186/s12985-022-01930-y. PMID:36443881; PMCID: PMC9702864.

16.Ebihara T, Matsubara T, Togami Y, Matsumoto H, Tachino J, Matsuura H, KojimaT, Sugihara F, Seno S, Okuzaki D, Hirata H, Ogura H. Combination of WFDC2,CHI3L1, and KRT19 in Plasma Defines a Clinically Useful Molecular Phenotype Associated with Prognosis in Critically Ill COVID-19 Patients. J Clin Immunol. 2023 Feb;43(2):286-298. doi: 10.1007/s10875-022-01386-3. Epub 2022 Nov 4. PMID: 36331721; PMCID: PMC9638294

17.Tachino J, Matsumoto H, Sugihara F, Seno S, Okuzaki D, Kitamura T, Komukai S,Kido Y, Kojima T, Togami Y, Katayama Y, Nakagawa Y, Ogura H. Development of clinical phenotypes and biological profiles via proteomic analysis of trauma patients. Crit Care. 2022 Aug 6;26(1):241. doi: 10.1186/s13054-022-04103-z. PMID: 35933364; PMCID: PMC9357328.

18.Togami Y, Matsumoto H, Yoshimura J, Matsubara T, Ebihara T, Matsuura H,Mitsuyama Y, Kojima T, Ishikawa M, Sugihara F, Hirata H, Okuzaki D, Ogura H. Significance of interferon signaling based on mRNA-microRNA integration and plasma protein analyses in critically ill COVID-19 patients. Mol Ther Nucleic Acids. 2022 Sep 13;29:343-353. doi: 10.1016/j.omtn.2022.07.005. Epub 2022 Jul 13. PMID: 35855895; PMCID: PMC9278015.

19.Nukiwa R, Oda S, Matsumoto H, Al Kadi M, Murao S, Matsubara T, Nakao S, Okuzaki D, Ogura H, Oda J. Changes in gene expression in healthcare workers during night shifts: implications for immune response and health risks. （J Intensive Care. 2025 Mar 11;13(1):14. doi: 10.1186/s40560-024-00769-5.）

20.Oda S, Matsumoto H, Togami Y, Yoshimura J, Ito H, Onishi S, Muratsu A, Mitsuyama Y, Okuzaki D, Ogura H, Tanaka S, Oda J. mRNA-miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia. Acute Med Surg. 2025 Apr 2;12(1):e70054. doi: 10.1002/ams2.70054.

21.Mitsuyama, Y., Matsumoto, H., Sugihara, F. et al. Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS. j intensive care 13, 26 (2025). https://doi.org/10.1186/s40560-025-00793-z

22.Tulyeu J, Søndergaard JN, Priest DG, Ebihara T, Matsumoto H, Llamas-Covarrubias MA, Imai M, Esaki S, Iwasaki S, Morita A, Yamazaki S, Sakaguchi S, Wing JB.Human precursor T follicular regulatory cells are primed for differentiation into mature Tfr and disrupted during severe infections.Sci Adv. 2025 Sep 26;11(39):eadv6939. doi: 10.1126/sciadv.adv6939.

23.Yoshinori Yokono, Takeshi Ebihara, Shinya Onishi, Yusuke Takahashi, Hisatake Matsumoto, Kentaro Shimizu, Satoshi Kutsuna, Jun Oda. Hemorrhagic shock and encephalopathy syndrome with hyper-inflammation and elevation of IL-6 and GDF-15 following COVID-19: A case report. IDCases 2025;Volume 42:e02390

24.Ito H, Ishikawa M, Yoshimura J, Liu Y, Sakakibara S, Sugihara F, Matsumoto H, Hirata H, Ogura H, Oda J, Okuzaki D. Neutrophil gene expression in COVID-19 patients with acute respiratory distress syndrome. Frontiers in Immunology.

25.Kishi Y, Liu YC, Ishikawa M, Yamashita M, Matsumoto H, Ogura H, Sakakibara S, Okuzaki D.
Mapping NK cell diversity in response to COVID-19 and mRNA vaccination.
Sci Rep. 2025 Oct 28;15(1):37577. doi: 10.1038/s41598-025-11575-w.

26.Nomura Y, Oda S, Matsumoto H, Togami Y, Shimazaki J, Okuzaki D, Ogura H, Oda J. Leukocyte mRNA sequencing reveals unfolded protein response activation in severe heat stroke in Japan. Front Cell Dev Biol. 2025 Nov 27;13:1640477. doi: 10.3389/fcell.2025.1640477.